Meta-Analysis of Genome-Wide Association Studies in > 80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels

Verfasser:	Dehghan, Abbas Dupuis, Josee Barbalic, Maja Bis, Joshua C. Eiriksdottir, Gudny Lu, Chen Pellikka, Niina Wallaschofski, Henri Kettunen, Johannes Henneman, Peter Baumert, Jens Strachan, David P. Fuchsberger, Christian Vitart, Veronique Wilson, James F. Pare, Guillaume Naitza, Silvia Rudock, Megan E. Surakka, Ida de Geus, Eco J. C. Alizadeh, Behrooz Z. Guralnik, Jack Shuldiner, Alan Tanaka, Toshiko Zee, Robert Y. L. Schnabel, Renate B. Nambi, Vijay Kavousi, Maryam Ripatti, Samuli Nauck, Matthias Smith, Nicholas L. Smith, Albert V. Sundvall, Jouko Scheet, Paul Liu, Yongmei Ruokonen, Aimo Rose, Lynda M. Larson, Martin G. Hoogeveen, Ron C. Freimer, Nelson B. Teumer, Alexander Tracy, Russell P. Launer, Lenore J. Buring, Julie E. Yamamoto, Jennifer F. Folsom, Aaron R. Sijbrands, Eric J. G. Pankow, James Elliott, Paul Keaney, John F. Sun, Wei Sarin, Antti-Pekka Fontes, Joao D. Badola, Sunita Astor, Brad C. Hofman, Albert Pouta, Anneli Werdan, Karl Greiser, Karin H. Kuss, Oliver Schwabedissen, Henriette E. Meyer Zu Thiery, Joachim Jamshidi, Yalda Nolte, Ilja M. Soranzo, Nicole Spector, Timothy D. Voelzke, Henry Parker, Alexander N. Aspelund, Thor Bates, David Young, Lauren Tsui, Kim Siscovick, David S. Guo, Xiuqing Rotter, Jerome I. Uda, Manuela Schlessinger, David Rudan, Igor Hicks, Andrew A. Penninx, Brenda W. Thorand, Barbara Gieger, Christian Coresh, Joe Willemsen, Gonneke Harris, Tamara B. Uitterlinden, Andre G. Jaervelin, Marjo-Riitta Rice, Kenneth Radke, Doerte Salomaa, Veikko van Dijk, Ko Willems Boerwinkle, Eric Vasan, Ramachandran S. Ferrucci, Luigi Gibson, Quince D. Bandinelli, Stefania Snieder, Harold Boomsma, Dorret I. Xiao, Xiangjun Campbell, Harry Hayward, Caroline Pramstaller, Peter P. van Duijn, Cornelia M. Peltonen, Leena Psaty, Bruce M. Gudnason, Vilmundur Ridker, Paul M. Homuth, Georg Koenig, Wolfgang Ballantyne, Christie M. Witteman, Jacqueline C. M. Benjamin, Emelia J. Perola, Markus Chasman, Daniel I.
Dokumenttyp:	Artikel
Erscheinungsdatum:	2011
Reihe/Periodikum:	Dehghan , A , Dupuis , J , Barbalic , M , Bis , J C , Eiriksdottir , G , Lu , C , Pellikka , N , Wallaschofski , H , Kettunen , J , Henneman , P , Baumert , J , Strachan , D P , Fuchsberger , C , Vitart , V , Wilson , J F , Pare , G , Naitza , S , Rudock , M E , Surakka , I , de Geus , E J C , Alizadeh , B Z , Guralnik , J , Shuldiner , A , Tanaka , T , Zee , R Y L , Schnabel , R B , Nambi , V , Kavousi , M , Ripatti , S , Nauck , M , Smith , N L , Smith , A V , Sundvall , J , Scheet , P , Liu , Y , Ruokonen , A , Rose , L M , Larson , M G , Hoogeveen , R C , Freimer , N B , Teumer , A , Tracy , R P , Launer , L J , Buring , J E , Yamamoto , J F , Folsom , A R , Sijbrands , E J G , Pankow , J , Elliott , P , Keaney , J F , Sun , W , Sarin , A-P , Fontes , J D , Badola , S , Astor , B C , Hofman , A , Pouta , A , Werdan , K , Greiser , K H , Kuss , O , Schwabedissen , H E M Z , Thiery , J , Jamshidi , Y , Nolte , I M , Soranzo , N , Spector , T D , Voelzke , H , Parker , A N , Aspelund , T , Bates , D , Young , L , Tsui , K , Siscovick , D S , Guo , X , Rotter , J I , Uda , M , Schlessinger , D , Rudan , I , Hicks , A A , Penninx , B W , Thorand , B , Gieger , C , Coresh , J , Willemsen , G , Harris , T B , Uitterlinden , A G , Jaervelin , M-R , Rice , K , Radke , D , Salomaa , V , van Dijk , K W , Boerwinkle , E , Vasan , R S , Ferrucci , L , Gibson , Q D , Bandinelli , S , Snieder , H , Boomsma , D I , Xiao , X , Campbell , H , Hayward , C , Pramstaller , P P , van Duijn , C M , Peltonen , L , Psaty , B M , Gudnason , V , Ridker , P M , Homuth , G , Koenig , W , Ballantyne , C M , Witteman , J C M , Benjamin , E J , Perola , M & Chasman , D I 2011 , ' Meta-Analysis of Genome-Wide Association Studies in > 80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels ' , Circulation , vol. 123 , no. 7 , pp. 731-738 . https://doi.org/10.1161/CIRCULATIONAHA.110.948570
Schlagwörter:	genetics / inflammation / meta-analysis / myocardial infarction / genome-wide association study / CORONARY-HEART-DISEASE / GENETICALLY ISOLATED POPULATION / NETHERLANDS TWIN REGISTER / EPIDEMIOLOGIC APPLICATIONS / COMMON VARIANTS / ALPHA-GENE / CRP GENE / DESIGN / FRAMINGHAM
Sprache:	Englisch
Permalink:	https://search.fid-benelux.de/Record/base-27209318
Datenquelle:	BASE; Originalkatalog
Powered By:	BASE
Link(s) :	https://hdl.handle.net/11370/1f16c9fe-a15e-4bae-91fe-ecea2e3dd6dc

Background-C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP levels. Methods and Results-We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population-based studies. We sought replication for the genome-wide significant and suggestive loci in a replication panel comprising 16 540 individuals from 10 independent studies. We found 18 genome-wide significant loci, and we provided evidence of replication for 8 of them. Our results confirm 7 previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2) or the immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1) or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found a significant interaction of body mass index with LEPR (P <2.9 x 10(-6)). A weighted genetic risk score that was developed to summarize the effect of risk alleles was strongly associated with CRP levels and explained approximate to 5% of the trait variance; however, there was no evidence for these genetic variants explaining the association of CRP with coronary heart disease. Conclusions-We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation. (Circulation. 2011; 123: 731-738.)